ABBV-383 for Multiple Myeloma

Recruiting at 56 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TeneoOne Inc.

Must be taking: Proteasome inhibitors, IMiDs, Anti-CD38

Must not be taking: BCMA-targeted therapy

Disqualifiers: Rapidly progressing disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests ABBV-383, a new drug for adults with multiple myeloma that has come back or not responded to other treatments. The drug is given through an IV regularly. The study will monitor the drug's effects and any side effects over several years.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug ABBV-383 for treating multiple myeloma?

Research shows that ABBV-383, a bispecific antibody targeting BCMA and CD3, has shown promising results in early human trials for patients with relapsed or hard-to-treat multiple myeloma. Similar treatments targeting BCMA have demonstrated the ability to effectively kill multiple myeloma cells and activate the immune system to fight the cancer. ^{1 2 3 4 5}

What is known about the safety of ABBV-383 for treating multiple myeloma?

In a phase I study, ABBV-383 was tested in patients with relapsed or refractory multiple myeloma, and the safety outcomes were reported. Additionally, a similar bispecific antibody, TNB-383B, showed mild increases in cytokines (proteins involved in cell signaling) associated with immune responses, suggesting some inflammatory effects but no severe safety concerns. ^{1 2 3 4 6}

What makes the drug ABBV-383 unique for treating multiple myeloma?

ABBV-383 is a novel bispecific antibody that targets both B-cell maturation antigen (BCMA) and CD3, effectively redirecting T cells to attack multiple myeloma cells. This dual-targeting approach is unique because it engages the body's own immune cells to specifically kill cancer cells, offering a promising option for patients with relapsed or refractory multiple myeloma. ^{1 3 4 5 6}

Research Team

TeneoOne Inc

Principal Investigator

TeneoOne Inc.

Eligibility Criteria

Adults with Multiple Myeloma that has returned or hasn't improved after treatment can join. They must have had at least 2-3 prior treatments, including specific drugs like proteasome inhibitors and anti-CD38 antibodies. For one part of the study, they shouldn't have had BCMA-targeted therapy before.

Inclusion Criteria

You must have a disease that can be measured according to the study guidelines.

I have never been treated with ABBV-383.

I've had 3+ treatments including PI, IMiD, and anti-CD38 for my condition.

Exclusion Criteria

I have received therapy targeting BCMA.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ABBV-383 as an infusion into the vein in 28 day cycles for approximately 3 years

3 years

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ABBV-383

Trial Overview The trial is testing ABBV-383, a new drug for relapsed/refractory Multiple Myeloma. It's given by IV in two parts: first finding the right starting dose then expanding to more patients; another group gets a fixed dose. The study lasts about 3 years with regular hospital visits.

Participant Groups

Group I: Arm C: ABBV-383 Step Up Experimental Treatment 1 Intervention

Participants will receive step up dose and full target dose of ABBV-383 in 28 day cycles.

Group II: Arm B: ABBV-383 BCMA Exposed Experimental Treatment 1 Intervention

Participants previously exposed to BCMA-targeted agents will receive ABBV-383 Dose A in 28 day cycles.

Group III: Arm A (Part 2): ABBV-383 Dose Expansion Experimental Treatment 1 Intervention

BCMA naïve participants will receive the dose of ABBV-383 dose A in 28 day cycles.

Group IV: Arm A (Part 1): ABBV-383 Dose Escalation Experimental Treatment 1 Intervention

B-cell maturation antigen (BCMA) naïve participants will receive different doses of ABBV-383 in 28 day cycles.

Who Is Running the Clinical Trial?

TeneoOne Inc.

Lead Sponsor

Trials

5

Recruited

860+

Findings from Research

ABBV-383, a bispecific antibody targeting B-cell maturation antigen and CD3, showed a promising overall response rate (ORR) of 68% in patients with relapsed/refractory multiple myeloma (RRMM) at doses of 40 mg or higher, indicating its potential efficacy as a treatment option.

The treatment was generally well tolerated, with common side effects including neutropenia (37%) and cytokine release syndrome (57%), and no deaths were deemed related to the study drug, suggesting a favorable safety profile for further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I First-in-Human Study of ABBV-383, a B-Cell Maturation Antigen × CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma. D'Souza, A., Shah, N., Rodriguez, C., et al.[2023]

Bispecific antibodies (BsAbs) and dual-targeted CAR T cells have shown promising results in treating relapsed/refractory multiple myeloma (RRMM) patients, particularly those who have not responded to at least three prior therapies.

Recent data from the 2023 ASCO annual meeting highlight that combinations targeting BCMA/CD3 and GPRC5D/CD3 lead to stronger and more durable responses in patients, indicating their potential effectiveness in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific antibodies and dual-targeting CAR-T cells for multiple myeloma: latest updates from the 2023 ASCO annual meeting. Hou, J., Li, Y., Lin, Q.[2023]

TNB-383B effectively induces the killing of plasma cells in bone marrow from patients with relapsed multiple myeloma, showing dose-dependent lysis starting at very low doses (0.001 μg).

The treatment leads to significant degranulation of cytotoxic T lymphocytes (CTLs) and modulates cytokine responses, with notable increases in IL-2/TNFα and IP10, indicating a robust immune response without significant T cell expansion or severe cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex vivo efficacy of BCMA-bispecific antibody TNB-383B in relapsed/refractory multiple myeloma. Foureau, DM., Bhutani, M., Robinson, M., et al.[2023]

The study developed several bispecific BCMA-CD3 antibodies that effectively target and kill multiple myeloma cells, demonstrating specific binding and cytotoxic activity in vitro with a strong affinity in the nanomolar range.

In vivo testing in a mouse model showed that these BCMA bispecific antibodies had high efficacy against multiple myeloma, supporting their potential for future clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific BCMA-CD3 Antibodies Block Multiple Myeloma Tumor Growth. Wu, L., Huang, Y., Sienkiewicz, J., et al.[2022]

The bispecific antibody BiFab-BCMA effectively redirects T cells to attack multiple myeloma cells, showing up to 20 times greater potency than a similar antibody targeting CS1.

BiFab-BCMA not only activates T cells in laboratory settings but also leads to rapid tumor regression in animal models, suggesting it could be a promising alternative to existing CAR-T therapies for treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-B cell maturation antigen bispecific antibody for multiple myeloma. Ramadoss, NS., Schulman, AD., Choi, SH., et al.[2015]

The fully human bispecific antibody REGN5458, which targets B-cell maturation antigen (BCMA) and CD3, effectively induces T-cell killing of multiple myeloma cells and shows strong antitumor activity in mouse models, demonstrating its potential as a rapid therapeutic option.

In head-to-head comparisons, REGN5458 cleared tumors more quickly than anti-BCMA CAR T cells, suggesting that bispecific antibodies can engage existing T cells at the tumor site for immediate action, while CAR T cells require time to activate and expand before they can attack the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A BCMAxCD3 bispecific T cell-engaging antibody demonstrates robust antitumor efficacy similar to that of anti-BCMA CAR T cells. DiLillo, DJ., Olson, K., Mohrs, K., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Phase I First-in-Human Study of ABBV-383, a B-Cell Maturation Antigen × CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Bispecific antibodies and dual-targeting CAR-T cells for multiple myeloma: latest updates from the 2023 ASCO annual meeting. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Ex vivo efficacy of BCMA-bispecific antibody TNB-383B in relapsed/refractory multiple myeloma. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Bispecific BCMA-CD3 Antibodies Block Multiple Myeloma Tumor Growth. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

An anti-B cell maturation antigen bispecific antibody for multiple myeloma. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

A BCMAxCD3 bispecific T cell-engaging antibody demonstrates robust antitumor efficacy similar to that of anti-BCMA CAR T cells. [2021]